FIBR: A Systems Approach to Study Redox Regulation of Functions of Photosynthetic Organisms

氧化还原稳态是光合生物如蓝藻和植物的核心功能。在本项目中，将采用系统方法来分析细胞氧化还原状态对这些生物体整体功能的影响。最初的重点将是蓝藻集胞藻6803，随后的应用在拟南芥，无血管植物，和立碗藓，非血管植物的生物学的理解。集胞藻6803基因组测序完整，适合高通量基因组水平操作。虽然集胞藻的基因、转录本和蛋白质的详细清单是可用的，但它不足以理解这种生物体复杂功能的组织层次。一个多学科的方法将被用来解决这一差距的基础知识。项目团队的专业知识涵盖分子遗传学、生物化学、蛋白质组学、代谢组学、计算生物学和系统工程，包括非线性建模、估计和药物分析。该团队的实验研究经验涵盖了蓝藻、苔藓和开花植物的模型系统。一个目的是推断一个基因调控网络在蓝藻，将包括识别的传感和信号通路。此外，一个基因调控网络将在拟南芥中独立产生，并将评估基因的保守性和相互作用。将对该网络进行验证，研究网络模块对整体氧化还原调节的贡献，并将该模型扩展到立碗藓。这种迭代过程有望产生对这些生物中氧化还原控制网络（RCN）的组织和功能的基本见解。此外，所提出的方法，即首先在蓝藻中建模RCN，然后将其扩展到植物，将突出这些过程在陆地plants.Broad影响的进化过程中的预期保守性：在这个项目中的研究活动将密切相关的本科生，研究生和博士后学生，和访问学者，无论是在华盛顿大学和高露洁大学的培训和发展。特别是，来自生物学和系统工程的学生将精通数学和计算方法的使用，以回答生物学中具有挑战性的问题。与琦玉大学的合作互动将允许美国和日本之间的科学互动和研究访问。该项目的一个重要目标是将尖端技术与学习经验相结合，这将激发缺乏重要研究项目的小型学院的教师和学生的发展。学生将获得指导，研究学分和培训。他们将意识到现代生命科学研究中迷人的活动和职业选择。基因组学、生物信息学和系统科学研究的实践培训将产生深远的教育影响，远远超出项目期间。http://www.sysbio.wustl.edu/

Redox homeostasis is central to the functions of oxygenic photosynthetic organismssuch as cyanobacteria and plants. In this project, a systems approach will beundertaken to analyze the impact of cellular redox status on the overall functions ofthese organisms. The initial focus will be on the cyanobacterium Synechocystis 6803,with subsequent applications in the understanding of the biology of Arabidopsis, avascular plant, and Physcomitrella, a non-vascular plant. Synechocystis 6803 has acompletely sequenced genome and is amenable to high-throughput genome levelmanipulations. Although the detailed inventory of the genes, transcripts and proteins areavailable for Synechocystis, it is inadequate to comprehend the organizational hierarchyof the complex functions of this organism. A multidisciplinary approach will be used toresolve this gap in fundamental knowledge. The expertise of the project team spansmolecular genetics, biochemistry, proteomics, metabolomics, computational biology andsystems engineering, which includes nonlinear modeling, estimation and statisticalanalysis. The experimental research experience of the team spans model systems incyanobacteria, moss and flowering plants. One aim is to infer a gene regulatory networkin cyanobacteria that will include identification of the sensing and signaling pathways. Inaddition, a gene regulatory network will be independently generated in Arabidopsis, andthe conservation of the genes and interactions will be evaluated. The network will bevalidated, the contribution of the network modules to the overall redox regulation will bestudied, and the model will be extended to Physcomitrella. Such an iterative process isexpected to generate fundamental insights into the organization and function of theredox control network (RCN) in these organisms. Furthermore, the proposed approach,viz. first to model an RCN in cyanobacteria and then to extend it to plants, will highlightthe expected conserved nature of these processes during the evolution of land plants.Broad Impact: The research activities in this project will be intimately connected to thetraining and development of undergraduate, graduate and post-doctoral students, andvisiting scholars, both at Washington University and Colgate University. In particular,students from both Biology and Systems Engineering will become well-versed in the useof mathematics and computational methods to answer challenging questions in biology.Collaborative interactions with Saitama University will allow scientific interactions andresearch visits between USA and Japan. An important goal of this project is anintegration of cutting-edge technologies with learning experiences that will inspire facultyand student development from small colleges lacking significant research programs.The students will obtain mentoring, research credit and training. They will becomeaware of the fascinating array of activities and career choices in modern life scienceresearch. Hands-on training in genomics, bioinformatics and systems science researchwill have far-reaching educational impacts well beyond the project period.The link for the project web site is http://www.sysbio.wustl.edu/.